rs148374607
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005051.3(QARS1):c.610G>A(p.Ala204Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A204V) has been classified as Uncertain significance.
Frequency
Consequence
NM_005051.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.610G>A | p.Ala204Thr | missense_variant | 7/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.577G>A | p.Ala193Thr | missense_variant | 7/24 | ||
QARS1 | XM_017006965.3 | c.610G>A | p.Ala204Thr | missense_variant | 7/23 | ||
QARS1 | NR_073590.2 | n.585G>A | non_coding_transcript_exon_variant | 7/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.610G>A | p.Ala204Thr | missense_variant | 7/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251490Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461882Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727242
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74360
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2021 | The c.610G>A (p.A204T) alteration is located in exon 7 (coding exon 7) of the QARS gene. This alteration results from a G to A substitution at nucleotide position 610, causing the alanine (A) at amino acid position 204 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 204 of the QARS protein (p.Ala204Thr). This variant is present in population databases (rs148374607, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with QARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 568125). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at